The Clinical Utility of a Precision Medicine Blood Test Incorporating Age, Sex, and Gene Expression for Evaluating Women with Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Analysis from the PRESET Registry.

Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry. Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing. Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1-40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16). Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation

Impact of \u3cem\u3eMYH6\u3c/em\u3e Variants in Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P \u3c 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P \u3c 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the β-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P \u3c 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P \u3c 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications

Health locus of control in patients undergoing coronary artery surgery – changes and associated outcomes: a seven-year cohort study

Introduction: Health locus of control is a measure of an individual’s beliefs in factors that are thought to determine health experiences. Scores are generated and form a graduated linear scale from external to internal control, with respect to their views on health causality. Health locus of control has been considered to be a relatively stable entity. However, it is not clear if this status changes in the advent of serious health challenges, such as coronary artery bypass graft surgery. The aim of this study is to explore the variability of health locus of control and its association with postoperative health in this context. Methods: In a longitudinal cohort study of patients undergoing coronary artery bypass graft surgery, a purposive sample (n=215) were recruited from the waiting list and followed up postoperatively, at approximately one year and seven years later. Results: Patients undergoing coronary artery bypass graft surgery demonstrated marked fluctuations in health locus of control in their peri-operative and rehabilitative phases. Mean health locus of control became more external (often associated with poorer outcomes) peri-operatively, and more internal (generally associated with better health outcomes) in the rehabilitative period. Conclusions: Health locus of control scores were shown to be changeable during a major health care intervention, with possible consequences for patient outcomes and care needs. The significant health belief upheaval demonstrated in this cohort should be considered in assessing patients preoperatively, and managed as part of the patients’ clinical journey by both acute and rehabilitation staff. It is likely to have particular importance in individualised assessment and management of future prevention advice for patients

An observational cohort feasibility study to identify microvesicle and miRNA biomarkers of acute kidney injury following paediatric cardiac surgery

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Objectives: Micro-RNA, small noncoding RNA fragments involved in gene regulation, and microvesicles, membrane-bound particles less than 1 μm known to regulate cellular processes including responses to injury, may serve as disease-specific biomarkers of acute kidney injury. We evaluated the feasibility of measuring these signals as well as other known acute kidney injury biomarkers in a mixed pediatric cardiac surgery population. Design: Single center prospective cohort feasibility study. Setting: PICU. Patients: Twenty-four children (≤ 17 yr) undergoing cardiac surgery with cardiopulmonary bypass without preexisting inflammatory state, acute kidney injury, or extracorporeal life support. Interventions: None. Measurements and Main Results: Acute kidney injury was defined according to modified Kidney Diseases Improving Global Outcomes criteria. Blood and urine samples were collected preoperatively and at 6–12 and 24 hours. Microvesicles derivation was assessed using flow cytometry and NanoSight analysis. Micro-RNAs were isolated from plasma and analyzed by microarray and quantitative real-time polymerase chain reaction. Data completeness for the primary outcomes was 100%. Patients with acute kidney injury (n = 14/24) were younger, underwent longer cardiopulmonary bypass, and required greater inotrope support. Acute kidney injury subjects had different fractional content of platelets and endothelial-derived microvesicles before surgery. Platelets and endothelial microvesicles levels were higher in acute kidney injury patients. A number of micro-RNA species were differentially expressed in acute kidney injury patients. Pathway analysis of candidate target genes in the kidney suggested that the most often affected pathways were phosphatase and tensin homolog and signal transducer and activator of transcription 3 signaling. Conclusions: Microvesicles and micro-RNAs expression patterns in pediatric cardiac surgery patients can be measured in children and potentially serve as tools for stratification of patients at risk of acute kidney injury

Choosing a Health Care Provider: The Role of Quality Information

Reviews research on the adequacy of the information available on provider quality; the type of information consumers seek in choosing physicians, physician groups, and hospitals; and their attitudes about, awareness of, and use of that information

Hospital Car Parking: The Impact of Access Costs

NHS Trusts have statutory powers to raise income, which allow them to decide whether to charge, and how much to charge, for hospital car parking. Trusts are not obliged to provide parking facilities on their premises, but provision will inevitably incur costs in the form of maintenance, security and staffing. If Trusts choose not to charge for parking, then these costs must be covered from other sources of revenue, potentially diverting resources from patient care. Charges typically account for around 0.25% of a hospital?s income, but can be as high as 1%. The government offers financial support to people on low incomes who incur travel expenses when accessing health care.

Safety of permanent pacemaker implantation: a prospective study

Although pacemaker implantation is considered to be low risk, it is not exempt from complications and technical failures during the procedure, both in the short and long term, and the complications that such patients may present remain unknown. The aim has been to analyze the complication rates associated with permanent pacing and to identify if these differ between patients with or without previous antithrombotic therapy. We used a prospective, single center, observational study of 310 adult patients with indications of permanent pacing. They were hospitalized from 1 January to 31 December 2014 and followed up for 6 months after the pacemaker implant. The participants were distributed into two groups according to the antithrombotic therapy prior to the implant. The most frequent major complications were pneumothorax (3.87%) and lead dislodgement (8.39%), while superficial phlebitis (12.90%) and uncomplicated hematomas (22.58%) were presented as the most recurrent minor complications. Hematomas were the most frequent minor complication in the antithrombotic therapy cohort, and shoulder pain was reported as the most recurrent minor complication in the non-exposed group. Finding out about complications in pacemaker implants enables a complete view of the process, and hence the prioritization of actions aimed at improving safety and reducing associated risks

Focal Spot, Winter 2009/2010

https://digitalcommons.wustl.edu/focal_spot_archives/1113/thumbnail.jp